The creation of vehicles for the effective delivery of hydrophobic anticancer drugs to tumor sites has garnered major attention in cancer chemotherapies for several decades. A successful strategy promises immense benefits to cancer sufferers through both the reduction of side-effects and a greater treatment efficacy. Current approaches focus on the use of nanocarriers, whereby the drug's pharmacokinetic properties and biodistribution profiles are manipulated by encapsulation within liposomes, polymeric nanoparticles or micelles, or by conjugation to hydrophilic polymers or inorganic nanomaterials. While these methods can be effective, there are concerns regarding the short-term and long-term toxicities arising from the synthetic nanomaterials other than the drug being delivered. This often leads to exhaustive preclinical evaluation and thus represents a difficult hurdle for the drug's translation into clinical use. Furthermore, there are inherent difficulties in achieving a quantitative and high drug loading per carrier, and the drug loading capacity varies depending not only on the carrier's properties but also on the type of drugs to be encapsulated or conjugated. Polydispersity, both in terms of polymer length and the amount of drug loaded or conjugated, is a critical issue susceptible to significant batch-to-batch variability. On the other hand, small molecule prodrugs are monodisperse but can be subject to rapid clearance and premature degradation
Many drugs, including chemotherapeutic drugs for cancer are well known for having low water solubility, for example, camptothecin and paclitaxel. To circumvent this, two strategies have been adopted—chemical modification of the drug to increase solubility or the use of a delivery vehicle. Camptothecin, a DNA-Topoisomerase I inhibitor that prevents DNA re-ligation during transcription and ultimately causes cell apoptosis, is not currently used in clinical cancer chemotherapy due to its very low water solubility and toxic side effects; however, its more soluble derivatives have successfully made the transition into clinical use, such as Topetecan HYCAMTIN, GlaxoSmithKline) and Irinotecan (CAMPTOSAR, Pfizer and CAMPTO, Yakult Honsha). These derivatives still cause significant side-effects due to non-selective modes of action, and would benefit from an improved delivery strategy. Paclitaxel, a mitotic inhibitor that stabilizes microtubules, preventing cell division and inducing apoptosis, has for many years been administered intravenously as a solution in Chremophor EL (CrEL), a formulation known as (TAXOL, Bristol-Myers Squibb). The Chremophor EL solvent, however, causes side-effects of its own in addition to those due to paclitaxel and alternatives are highly desired. In 2005, an injectable formulation of paclitaxel in which the drug is bound to the protein albumin was approved for use by the FDA. Known as (ABRAXANE, Celgene), this mode of delivery represents the first nanoparticle albumin bound (nab) technology platform. While the carrier causes little to no side-effects, those due to the paclitaxel are still present.
As such, there still exists a need for improved compositions and methods for solubilizing drug compounds that have low water solubility without inducing unwanted secondary biological effects due to the solubilization methods.